MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3

Int J Cancer. 2011 Apr 15;128(8):1758-69. doi: 10.1002/ijc.25509.


Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA-125b (miR-125b) was implicated to have close relationship with cell proliferation and differentiation, and downregulation of miR-125b was observed in various types of cancers. However, the biological function of miR-125b in bladder tumorigenesis is still unknown. In our study, we showed that the expression of miR-125b was significantly decreased in bladder cancer tissues and four bladder cancer cell lines. Moreover, miR-125b could suppress bladder cancer cells to form colonies in vitro and to develop tumors in nude mice. E2F3, which was critical for G1/S transition and was overexpressed in most of poor-differentiated bladder cancers, was identified as a target of miR-125b by luciferase assay. The E2F3 mRNA and protein expression levels were detected in bladder cancer tissues and cell lines, and interestingly, inverse correlations between miR-125b and E2F3 protein level were found in bladder cancer tissues and four E2F3 nonamplified cell lines. Introduction of miR-125b could reduce the expression of E2F3 protein but not the E2F3 mRNA. In addition, we observed that transfection of miR-125b could inhibit the expression of Cyclin A2, one of the E2Fs-responsive genes involved in G1/S transition. These results suggest that miR-125b may regulate G1/S transition through the E2F3-Cyclin A2 signaling pathway. Taken together, miR-125b may act as a tumor suppressor in bladder urothelium, and downregulation of miR-125b may contribute to the tumorigenesis of bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / prevention & control*
  • Cell Cycle
  • Cell Proliferation
  • Cyclin A2 / metabolism
  • Down-Regulation
  • E2F3 Transcription Factor / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Luciferases / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / physiology*
  • Middle Aged
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / prevention & control*


  • Cyclin A2
  • E2F3 Transcription Factor
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Luciferases